Orientia tsutsugamushi Ank5 promotes NLRC5 cytoplasmic retention and degradation to inhibit MHC class I expression.
Orientia tsutsugamushi
/ metabolism
Humans
Intracellular Signaling Peptides and Proteins
/ metabolism
Histocompatibility Antigens Class I
/ metabolism
Animals
Bacterial Proteins
/ metabolism
Cytoplasm
/ metabolism
HEK293 Cells
Proteolysis
Scrub Typhus
/ immunology
Mice
Ubiquitination
Host-Pathogen Interactions
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 Sep 2024
14 Sep 2024
Historique:
received:
14
09
2023
accepted:
27
08
2024
medline:
15
9
2024
pubmed:
15
9
2024
entrez:
14
9
2024
Statut:
epublish
Résumé
How intracellular bacteria subvert the major histocompatibility complex (MHC) class I pathway is poorly understood. Here, we show that the obligate intracellular bacterium Orientia tsutsugamushi uses its effector protein, Ank5, to inhibit nuclear translocation of the MHC class I gene transactivator, NLRC5, and orchestrate its proteasomal degradation. Ank5 uses a tyrosine in its fourth ankyrin repeat to bind the NLRC5 N-terminus while its F-box directs host SCF complex ubiquitination of NLRC5 in the leucine-rich repeat region that dictates susceptibility to Orientia- and Ank5-mediated degradation. The ability of O. tsutsugamushi strains to degrade NLRC5 correlates with ank5 genomic carriage. Ectopically expressed Ank5 that can bind but not degrade NLRC5 protects the transactivator during Orientia infection. Thus, Ank5 is an immunoevasin that uses its bipartite architecture to rid host cells of NLRC5 and reduce surface MHC class I molecules. This study offers insight into how intracellular pathogens can impair MHC class I expression.
Identifiants
pubmed: 39277599
doi: 10.1038/s41467-024-52119-6
pii: 10.1038/s41467-024-52119-6
doi:
Substances chimiques
NLRC5 protein, human
0
Intracellular Signaling Peptides and Proteins
0
Histocompatibility Antigens Class I
0
Bacterial Proteins
0
NLRC5 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8069Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : 1R01 AI123346
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : 2R56 AI123346
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : 1F32 AI174656A1
Organisme : Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)
ID : 1R01 AI167857
Organisme : American Heart Association (American Heart Association, Inc.)
ID : 20PRE35210610
Informations de copyright
© 2024. The Author(s).
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